Adjuvants are substances which, when administered along with an antigen, enhance the immune response of the organism. The adjuvants used in vaccine formulations aim at triggering the immune response by administering the smallest amount of antigen possible and, therefore, avoiding any possible risks deriving from an exposure to massive doses of antigen. The vaccine procedure, performed in this manner, promotes the formation of an immune memory capable of priming a “secondary response” for its specificity and memory, and allows the organism to recognise a foreign antigen with lower efficiency and rapidity in the course of repeated exposures. The secondary response, based on the presence of pre-formed antibodies and on a greater frequency of cells specific to a given antigen, allows the quick elimination of the pathogen (from which the antigen is derived) and prevents the physio-pathological processes on which the diseases induced by the pathogen itself are based. As such, adjuvants are indispensable components in the formulation of vaccines, and have in fact been the necessary requirement for the formulation of modern vaccine formulations. For example, they are present in the formulations of vaccines against hepatitis A and B, human papilloma virus (HPV), against B-type Haemophilus influenzae, against pneumococcal infections and many others.
Adjuvants, despite increasing the duration and intensity of immune response, cause neither specific nor long-lasting effects on the immune system. Furthermore, they may also be used for other purposes, such as the reduction of toxicity or improvement of stability of multiple component vaccines. For these reasons, the selection of the adjuvant is often crucial for the use of modern vaccines which often contain natural or synthetic antigen substances so as to avoid the problems induced by the use of attenuated or inactivated pathogens.
Currently, the adjuvants of human vaccines more commonly used are aluminium salts, typically aluminium hydroxide, aluminium phosphate and potassium and aluminium sulphate.
More recently, the principles of innate immunity have been used to develop new classes of adjuvants which comprise various types of oil emulsions or liposomes, bacterial products such as lipid A, viral products and saponins.
For many of these substances, although the exact mechanism of action is not known, there are evidence suggesting that they act through recruitment and activation effects of cells of the innate immune system, improving the capability of processing and presenting antigens by cells specifically aimed at triggering the specific immune response, or even specific targeting mechanisms or storage effects. Recently, a great impulse to the identification and development of new adjuvants has been determined by the need of reducing toxicity in vaccines containing highly purified antigens and vaccines against chronic diseases, such as for example HIV, parasitary disease, and certain tumour forms.
Alpha-sulphoquinovosides are known which are present in all photosynthetic organisms, such as algae and terrestrial plants. (H. DANIEL, et al. 1961. The plant sulfolipid. Identification of 6-sulfo quinovose, JACS, 83, 1765-1766; M. LEPAGEH, et al. 1961. The Plant Sulfolipid. Isolation and Properties of Sulfoglycosyl Glycerol, JACS, 83, 157-159; M. MIYANO, et al. 1962.The Plant Sulfolipid. VI. Configuration of the Glycerol Moiety, JACS, 84, 57-58; L. Y. Okaya, 1964. The plant sulfolipid: a crystallographic study. Acta Cryst. 17, 1276-1282; Frank D. et al., The Lipid Handbook 3rd Edition, CRC Press, Boca Raton, 2007, pp. 123-128).
Currently, therefore there is a strong need of physiologically acceptable substances which find application as vaccine adjuvants.
It is an object of the present invention to find substances which are suitable as pharmaceutically acceptable adjuvants in vaccine formulations.